USPTO Patents Application 10687850

(19)

(12)

Europdisches Paten tamt
European Patent Office
Office europeen des brevets (11) EP 0 878 713 A2

EUROPEAN PATENT APPLICATION

(43) Date of publication:

18.11.1998 Bulletin 1998/47

(21) Application number: 98107778.7

(22) Date of filing: 29.04.1 998

(51) IntCI. 6 : G01N 33/487, G01N 33/49,
G01N 27/327

(84) Designated Contracting States:

• Tudor, Brenda L.

AT BE CH CY DE DK ES R FR GB GR IE IT LI LU

Elkhart, Indiana 46514 (US)

MCNL PTSE

• Yip, Kin-Fai

Designated Extension States:

Elkhart, Indiana 46516 (US)

ALLTLVMKRO SI

(74) Representative:

(30) Priority: 12.05.1997 US 854440

Drope, Rudiger, Dr. et al

c/o Bayer AG

(71) Applicant: Bayer Corporation

Konzernbereich RP

Pittsburgh, PA 15205-9741 (US)

Patente und Lizenzen

(72) Inventors:

51368 Lever kusen (DE)

• Huang, Dijia

Granger, Indiana 46530 (US)

CM
<
CO

T-

CO
00

o

Q.

LU

(54) Method and apparatus for correcting ambient temperature effect in biosensors

(57) A method and apparatus are provided for cor*
recting ambient temperature effect in biosensors. An
ambient temperature value is measured. A sample is
applied to the biosensors, then a current generated in
the test sample is measured. An observed analyte con-
centration value is calculated from the current through a
standard response curve. The observed analyte con-
centration is then modified utilizing the measured ambi-
ent temperature value to thereby increase the accuracy
of the analyte determination. The analyte concentration
value can be calculated by solving the following equa-

tion:

-(T 2 2 -24 2 )*I2-(T 2 -24)*I1
fT 2 2 -24 2 )*S2 + (T 2 -24)*S1 +1

where G-| is said observed analyte concentration value,
T 2 is said measured ambient temperature value and 11 ,
12, S1, and S2 are predetermined parameters.

MEMORY
104

100

THERMISTOR
122

110-
112-

120 "

SENSOR
108

METER
106

ON/OFF
INPUT

SYSTEM
FEATURE
INPUT

TEMPERATURE
READING

MICROPROCESSOR
102

ALARM
162

DISPLAY
150

DATA
PORT
164

FIG.1

BATTERY
MONITOR
160

Printed by Xercct (UK) Business Services
2.16.6/3.4

EP 0 878 713 A2

Description

Held of the Invention

The present invention relates to a biosensor, and, more particularly, to a new and improved method and apparatus
for conecting ambient temperature effect in biosensors.

Description of the Prior Art

The quantitative determination of analytes in body fluids is of great importance in the diagnoses and maintenance
of certain physiological abnormalities. For example lactate, cholesterol and bilirubin should be monitored in certain indi-
viduals. In particular, the determination of glucose in body fluids is of great importance to diabetic individuals who must
frequently check the level of glucose in their body fluids as a means of regulating the glucose intake in their diets. While
the remainder of the disclosure herein will be directed towards the determination of glucose, it is to be understood that
the procedure and apparatus of this invention can be used for the determination of other analytes upon selection of the
appropriate enzyme. The ideal diagnostic device for the detection of glucose in fluids must be simple, so as not to
require a high degree of technical skill on the part of the technician administering the test. In many cases, these tests
are administered by the patient which lends further emphasis to the need for a test which is easy to carry out. Addition-
ally, such a device should be based upon elements which are sufficiently stable to meet situations of prolonged storage.

Methods for determining analyte concentration in fluids can be based on the electrochemical reaction between an
enzyme and the analyte specific to the enzyme and a mediator which maintains the enzyme in its initial oxidation state.
Suitable redox enzymes include oxidases, dehydrogenases, catalase and peroxidase. For example, in the case where
glucose is the analyte, the reaction with glucose oxidase and oxygen is represented by equation (A).

glucose + 0 2 g^^xidase(GO) gjuconoladQne + ^ (A)

In a colorimetric assay, the released hydrogen peroxide, in the presence of a peroxidase, causes a color change in
a redox indicator which color change is proportional to the level of glucose in the test fluid. While colorimetric tests can
be made semi-quantitative by the use of color charts for comparison of the color change of the redox indicator with the
color change obtained using test fluids of known glucose concentration, and can be rendered more highly quantitative
by reading the result with a spectrophotometric instrument, the results are generally not as accurate nor are they
obtained as quickly as those obtained using an electrochemical biosensor. As used herein, the term biosensor is
intended to refer to an analytical device that responds selectively to analytes in an appropriate sample and converts
their concentration into an electrical signal via a combination of a biological recognition signal and a physico-chemical
transducer. Aside from its greater accuracy, a biosensor is an instrument which generates an electrical signal directly
thereby facilitating a simplified design. Furthermore, a biosensor offers the advantage of low material cost since a thin
layer of chemicals is deposited on the electrodes and little material is wasted.

H 2 0 2 ->0 2 + 2H + + 2e" (B)

The electron flow is then converted to the electrical signal which directly correlates to the glucose concentration.

In the initial step of the reaction represented by equation (A), glucose present in the test sample converts the oxi-
dized flavin adenine dinucleotide (FAD) center of the enzyme into its reduced form, (FADH2). Because these redox
centers are essentially electrically insulated within the enzyme molecule, direct electron transfer to the surface of a con-
ventional electrode does not occur to any measurable degree in the absence of an unacceptably high overvoltage. An
improvement to this system involves the use of a nonphysiological redox coupling between the electrode and the
enzyme to shuttle electrons between the (FADH2) and the electrode. This is represented by the following scheme in
which the redox coupler, typically referred to as a mediator, is represented by M:

Glucose + GO(FAD) -> gluconolactone + GOfFADH^

GO(FADH 2 ) + 2M ox -> GO(FAD) + 2M rQdt + 2H+

2M red -* 2M ox + 2 ©~ (at the electrode)

In this scheme, GO(FAD) represents the oxidized form of glucose oxidase and GOCFADhy indicates its reduced
form. The mediating species M red shuttles electrons from the reduced enzyme to the electrode thereby oxidizing the
enzyme causing its regeneration in situ which, of course, is desirable for reasons of economy. The main purpose for

EP0878 713A2

using a mediator is to reduce the working potential of the sensor. An ideal mediator would be re-oxidized at the elec-
trode at a low potential under which impurity in the chemical layer and interfering substances in the sample would not
be oxidized thereby minimizing interference.

Many compounds are useful as mediators due to their ability to accept electrons from the reduced enzyme and
transfer them to the electrode. Among the mediators known to be useful as electron transfer agents in analytical deter-
minations are the substituted benzo- and naphthoquinones disclosed in U.S. Patent 4,746.607; the N-oxides, nitroso
compounds, hydroxylamines and oxines specifically disclosed in EP 0 354 441 ; the flavins, phenazines, phenothi-
azines, indophenols, substituted 1,4-benzoquinones and indamins disclosed in EP 0 330 517 and the phenazin-
iumfthenoxazinium salts described in U.S. Patent 3,791 ,988. A comprehensive review of electrochemical mediators of
biological redox systems can be found in Analytica Clinica Acta . 140 (1982), Pp 1-18.

Among the more venerable mediators is hexacyanoferrate, also known as ferricyanide, which is discussed by
Schlapfer et al in Clinica Chimica Acta .. 57 (1974), Pp. 283-289. In U.S. Patent 4,929,545 there is disclosed the use of
a soluble ferricyanide compound in combination with a soluble ferric compound in a composition for enzymaticaliy
determining an analyte in a sample. Substituting the iron salt of ferricyanide for oxygen in equation (A) provides:

Glucose + 2 Fe w (CN) 3 ' 6 — gluconolactone + 2 Fe^CN) 4 ^

since the ferricyanide is reduced to ferrocyanide by its acceptance of electrons from the glucose oxidase enzyme.
Another way of expressing this reaction is by use of the following equation (C):

Glucose + GO(FAD) Gluconolactone + GO(FADH 2 ) (C)

GO(FADH 2 ) + 2 FE(CN 3 ) 3 ' 6 -> GO(FAD) + 2 FE(CN) 6 4 -+ 2H +

2 FEfCNJg 4 *-* 2 FEfCNJe 3 * + 2e' (at the electrode)

The electrons released are directly proportional to the amount of glucose in the test fluid and can be related thereto by
measurement of the current which is produced upon the application of a potential thereto. Oxidation of the ferrocyanide
at the anode renews the cycle.

Summary of the Invention

Important objects of the present invention are to provide a new and improved method and apparatus for correcting
ambient temperature effect in biosensors; to provide such method and apparatus that eliminates or minimizes the ambi-
ent temperature effect in analyte concentration value identified by a biosensor; and to provide such method and appa-
ratus that overcome many of the disadvantages of prior art arrangements.

In brief, a method and apparatus are provided for correcting ambient temperature effect in biosensors. An ambient
temperature value is measured. A sample is applied to the biosensors, then a current generated in the test sample is
measured. An observed analyte concentration value is calculated from the current through a standard response curve.
The observed analyte concentration is then modified utilizing the measured ambient temperature value to thereby
increase the accuracy of the analyte determination.

In accordance with a feature of the invention, the analyte concentration value is calculated by solving the following
equation:

Q u G 1 -(T 2 2 -24 2 )*I2-(T 2 -24)M1
2 (T 2 2 -24 2 )*S2 + (T 2 -24)*S1 + 1

where G n is said observed analyte concentration value, T 2 is said measured ambient temperature value and 11 , 12, S1 ,
and S2 are predetermined parameters.

Brief Description of the Drawing

The present invention together with the above and other objects and advantages may best be understood from the
following detailed description of the preferred embodiments of the invention illustrated in the drawings, wherein:

FIG. 1 is a block diagram representation of biosensor in accordance with the present invention;

EP 0 878 713 A2

FIG. 2 is a flow chart illustrating logical steps performed in accordance with the present invention of the method cor-
recting ambient temperature effect in biosensors by the biosensor of FIG. 1 .

Detailed Description of the Preferred Embodiments

Having reference now to the drawings, in ^■^^^^^^'Z^^m'S^^S
desionated as a whole by the reference character 100 and arranged in accordance w.th pr.nc.ples of the present .nven-
SToSso, System 100 -dudes a microprocessor 102 together with an assodat^^
and user data. A meter function 1 06 coupled to biosensor 108 is operatively control fed by the m^c^sor l^for
Recording test values, such as blood glucose test values. An ON/OFF input at a l.ne 110 responsive to toe user ON/OFF
Z ojerafon is coupled to the micrVocessor 102 for r^rforming me blood test sequence ^
mA?ystem features input at a line 1 1 2 responsive to a user input operation is coupled to the m ' cro ^^ r u 2 i °f 1 f ^
selectively performing the system features mode of biosensor 100. A srgnal .nput .nd.cated at a line 120 .s cc «Mto
?he microprocessor io2 providing temperature information from a thermistor 122 ,n accordance ^ the imrantion.
Microprocessor 102 contains suitable programming to perform toe metres

A display 150 is coupled to the microprocessor 102 for displaying information to the user .nclud.ng t^t resu to A
battery monitor function 160 is coupled to the microprocessor 102 for detecting a low or dead bO^«n«n An
alarm function 162 is coupled to the microprocessor 102 for detecting predefined system condrtions and for generating
alarm So* Tfor the user of bicsenso? system 100. A data port or communications interface 164 couples data to

20 ^ ESSE? l^XtSuce the temperature bias, b^sensor system 100 performs a temperature

^StolS* 6 in accordance wKh the method for correcting ambient temperature
effect?boielrs108bytoe biosensor processor 102 begin at block 200. First a-rtiemterrperato^^
x £ ed aTa bb* 202 lieled MEASURE INSTRUMENT TEMPERATURE T2. Tnen sensor ^ -/""^ "
ndicated at a block 204. Next the measured cunent value is converted into an analyte concentration value, such as g^-
SrScer^tion value (observed concentration), as irxficated at a block 206. Then correcf,on for terrperature effe^
teperformed inafinal glucose concentration calculation as indicated at a block 208. The temperature corrected glucose
concentration is calculated utilizing the following equation:

10

15

30

G 1 -(T ! , 2 -24 2 )-l2-(T 2 -24)-|1

Go —

2 (T 2 2 -24VS2 + (T 2 -24)*S1+1

35

40

45

50

55

where G, is said observed analyte concentration value. T 2 is said measured ambient temperature value and 11 , 12. S1 .
and S2 are Dredetermined parameters. This completes the sequence as indicated at a block 210.

S^eSrTc b™se" ors 108 are known to be sensitive to temperature. This temperature effect occurs because
diffusion of the mediator to the working electrode is temperature dependent. Diffusion typically induces a temperature
effect of 1 -2% bias per degree centigrade. Therefore temperatures as low as ^^^^'^^^
ofSuiWamiternperaTures as high as40»C would produce resutewfth a bias about

ment provides results between 0 to 50°C. The only available temperature measurement comes from a t^"*"™*
toeinstrument In order to reduce the temperature bias it was necessary to develop a temperature correction algorithm.

Z tempe 2e effect was determined experimentally by biosensor system 1 00 whole blood ^9'^ ^rover
the entire glucose (50 to 600 rngftlL) and temperature range (10 to 40«C) expected to be encountered. Actual Wood glu-
LtS ^e temperatures wSe measured. This was done for six different sensor ™
W>und interest" temperature correction method was used, several lots had percent b.ases of -1 0% to -1 3% at the
extreme temperatures. The formula for the "compound interest" correction method is:

G 2 =G 1 *(1 + tc/100) &T Equation 1

where G, is the observed glucose concentration, tc is the temperature coefficient determined experimentally and T is

^ S^oSweresr algorithm did not workwell because toe temperature co^

concentration A "polynomial" conection algorithm was invented to handle the varying temperature coeff .crent problem

S usCa POlynS conectton algorHhm, toe perce^ b^

SaLnelnmethod is descrtoed in Equation #2. The grand sum of the ^* b ™^™f^**™
the polynomial correction method had less overall bias. Also, at the very extreme temperatures of 2 and 49 C, the pol

4

EP0 878 713 A2

ynomial correction method had lower bias (below 13.5%) where as the compound interest method was as high as -25%.

Therefore, the polynomial correction method provided an improvement over the "compound interest" correction
method.

After running the glucose assay at different temperatures the current response at each temperature was calculated
5 through the 24°C (sample temperature) standard response curve to obtain the observed glucose concentratioa

The observed glucose concentration and the sample temperature were then used to calculate the corrected glu-
cose concentration using the following equation:

10 r G i-CT 2 2 -24Vl2-(T 2 -24ri1

w G 2 = — - - Equation 2

(T 2 2 -24VS2 + (T 2 -24)*S1 + 1

where is the observed glucose concentration, T 2 is the sample temperature and 11 , 12, S1 , and S2 are the predeter-
15 mined coefficients. These coefficients were determined experimentally. See the following exemplary procedure for
details.

Table 1 shows an example of the temperature correction results. T 2 is the sample temperature. G R is the reference
glucose valve. I is the measured current. G-| is the observed glucose concentration (without temperature correction).
%B is the percent bias without temperature correction. is the temperature corrected glucose concentration. %B C is
20 the percent bias after temperature correction.

The data shows the percent bias before and after the correction algorithm was applied. The algorithm and coeffi-
cients were able to reduce the percent bias at the extreme temperatures of 10 to 40°C to within +/-7%.

25

30

35

40

45

50

55

5

EXAMPLE

EP 0 878 713 A2

10

15

20

25

30

35

Table l: Temperature Correction for Lot C

II
12
SI
S2

Lot C

T 2

8.7
8.7
8.7
8.7
8.7
16.7
16.7
16.7
16.7
16.7
23.9
23.9
23.9
23.9
23.9
30.6
30.6
30.6
30.6
30.6
38.2
38.2
38.2
38.2
38.2

50
100
200
400
600

50
100
200
400
600

50
100
200
400
600

50
100
200
400
600

50
100
200
400
600

0.17706
-0.0086
0.01529
0.00004

%B

G 2

1024
1484
2404
4243
6082
1109
1608
2606
4602
6598
1158
1729
2871
5155
7439
1212
1851
3128
5682
8236
1251
2008
3522
6550
9578

38.3

78.6
159.1
320.1
481.2

45.7

89.4
176.8
351.6
526.4

50.0
100.0
200.0
400.0
600.0

54.7
110.6
222.5
446.1
669.8

58.1
124.4
257.0
522.1
787.3

-23.4%
-21.4%
-20.5%
-20.0%
-19.8%
-8.6%
-10.6%
-11.6%
-12.1%
-12.3%
0.0%
0.0%
0.0%
0.0%
0.0%
9.5%
10.6%
11.2%
11.5%
11.6%
16.2%
24.4%
28.5%
30.5%
31.2%

49.1
102.9
210.6
426.0
641.4

50.6
100.4
199.9
398.9
597.9

50.0
100.0
200.0
400.0
600.0

50.8
100.8
200.9
401.1
601.3

50.4
103.3
209.0
420.4
631.8

%B C

-1.8%
2.9%
5.3%
6.5%
6.9%
1.3%
0.4%
0.0%
-0.3%
-0.3%
0.0%
0.0%
0.0%
0.0%
0.0%
1.5%
0.8%
0.5%
0.3%
0.2%
0.8%
3.3%
4.5%
5.1%
5.3%

40

45

50

The following describes an exemplary procedure used for determining the temperature correction coefficients (L
2 ' ^« % 10 Equation 2) - Rrst venous heparinized whole Wood (~45% hematocrit) from a single donor was spiked close
to different glucose concentrations (values determined by the Yellow Springs Instrument, YSI. reference method and
corrected for any known sample interferences) and tested in system 100 instruments at different environmental cham-
ber temperatures (Table 1, e.g. samples of 50 and 400 mg/dL glucose at 8.7, 16.7, 23.9, 30.6 and 38.2*C X .) The Yellow
Springs Instrument and method are described by Conrad et a)., in the February 1989 "Journal of Pediatrics" Pages 281 -
287 and by Burmeister et al., in "Analytical Letters", 28(4), 581-592 (1995). High relative humidity (65 to 85%) was
ma.nta.ned in the chamber in order to prevent evaporative cooling, and the sample was equilibrated to the chamber
temperature; this way the temperature effect would result only from the chemistry. The actual sample temperature was
measured for each glucose spike. To determine the sample temperature, a 0.0005" thermocouple was inserted into a
sensor without chemistry, and temperature data was collected every second after the blood was added to the sensor

55

6

EP 0 878 713 A2

Table 2

15

Lot C Actual YSI Glucose and Current Response

Sample Temp.

YSI

Current

Slope

Intercept

8.7°C

54.2

1063

8.7°C

412.5

4358

9.20

564.6

16.7°C

54.9

1148

16.7°C

414.9

4750

9.98

610.2

23.9°C

55.7

1223

23.9°C

418

5359

11.42

587.1

30.6oC

49.3

1203

30.6OC

408 4

5787

12.77

573.7

38.2oC

51.6

1275

38.2oC

418.7

6833

15.14

493.8

Next, the current response at exactly 50, 100, 200, 400, and 600 mg/dL glucose for each temperature was deter-
mined through the curves using the slope and intercepts determined in Table 2. Using these calculated current values
the observed glucose concentration was determined through the 24°C curve as provided in Table 3.

25

Table 3

30

Lot C - Current Through the YSI 50 and 400 mg/dL Curves and the Observed Glucose mg/dL

Through the 24°C Curve

Sample Temperature °C

YSI Reference Glucose
mg/dL

Current

23.9°C Curve Observed
Glucose mg/dL

8.7

50

1024

38.3

35

8.7

100

1484

78.6

8.7

200

2404

159.1

87

400

4243

320.1

8.7

600

6082

481.2

40

16.7

50

1109

45.7

16.7

100

1608

89.4

16.7

200

2606

176.8

45

16.7

400

4602

351.6

16.7

600

6598

526.4

23.9

50

1158

50.0

23.9

100

1729

100.0

50

23.9

200

2871

200.0

23.9

400

5155

400.0

23.9

600

7439

600.0

55

30.6

50

1212

57.7

30.6

100

1851

110.6

30.6

200

3128

222.5

7

EP 0 878 713 A2

Table 3 (continued)

Lot C - Current Through the YSI 50 and 400 mg/dL Curves and the Observed Glucose mg/dL
Through the 24°C Curve

5

Sample Temperature °C

YSI Reference Glucose
mg/dL

Current

23.9°C Curve Observed
Glucose mg/dL

30.6

400

5682

446.1

30.6

600

8236

669.8

10

38.2

50

1251

58.1

38.2

100

2008

124.4

38.2

200

3522

257.0

15

38.2

400

6550

522.1

38.2 J

600

9578

787.3

25

30

Table 4

35

45

50

55

LotC

■ 2nd Order Polynomial Coefficients

Coefficient

50 mg/dL

100 mg/dL

200 mg/dL

400 mg/dL

600 mg/dL

a0

29.689

68.654

146.318

301.709

457.305

a1

1.08071

1.06138

1.04494

1.00696

0.95187

a2

-0.00881

0.01035

0.04829

0.12417

0.20045

Corr.Coef.R

0.9990

1.000

0.9998

0.9996

0.9995

vJUZZL ^ ? f0r *" different levelS of 9lucose were P |otled the glucose concentration The date

G 1= (T 2 Va2 + T 2 *a1+a0
And at a sample temperature of 24°C, G2 (Corrected) = G-j (Observed)

G 2 = (24 2 ra2 + 24*a1+a0
Subtracting equation (3) from equation (2) gives:

G 2 - G , = (T 2 2 . 24 2 )*a2 + (T 2 - 24)*a1
From the linear plots generated at steps 4 and 5:

al =SrG 2 + h

Or Equation 3

Or Equation 4

Equation 5

Equation 6

8

EP0 878 713 A2

and

a2 = S2*G 2 + t2 Equation 7

5 Combining equation (5), (6), and (7) gives equation (2).

While the present invention has been described with reference to the details of the embodiments of the invention
shown in the drawing, these details are not intended to limit the scope of the invention as claimed in the appended
claims.

w Claims

1 . A method for correcting ambient temperature effect in biosensors comprising the steps of:

measuring an ambient temperature value;
15 applying a sample to the biosensors and measuring a current generated in the test sample;

calculating an analyte concentration value utilizing said measured ambient temperature value to thereby
increase the accuracy of the analyte determination.

2. A method for correcting ambient temperature effect in biosensors as recited in claim 1 wherein the step of calculat-
20 ing said analyte concentration value includes the step of converting said measured current to an observed analyte

concentration value and calculating a corrected analyte concentration value utilizing the equation:

G 1 -(T 2 2 -24 2 )M2>(T 2 -24)M1

25 2 (T 2 2 -24V S2 + {T 2 -24)*S1 + 1

where is said observed analyte concentration value, T 2 is said measured ambient temperature value and 11, 12,
S1 , and S2 are set values.

30

3. A method for correcting ambient temperature effect in biosensors as recited in claim 2 wherein 11 , 12, S1 , and S2
are experimentally determined coefficients.

4. A method for correcting ambient temperature effect in biosensors as recited in claim 1 wherein the analyte is glu-
35 cose.

5. A method for correcting ambient temperature effect in biosensors as recited in claim 1 wherein the step of calculat-
ing said analyte concentration value includes the step of solving a polynomial equation; said polynomial equation
including said measured ambient temperature value.

40

6. A method for correcting ambient temperature effect in biosensors as recited in claim 5 wherein said polynomial
equation includes a converted measured current value and predefined experimentally determined coefficients.

7. Apparatus for correcting ambient temperature effect in biosensors comprising:

45

means for measuring an ambient temperature value;

means responsive to an applied sample to the biosensors, for measuring a current generated in the test sam-
ple; and

means for calculating an analyte concentration value utilizing said measured ambient temperature value to
so thereby increase the accuracy of the analyte determination.

8. Apparatus for correcting ambient temperature effect in biosensors as recited in claim 7 includes processor means
for performing a predefined test sequence; and wherein said means for measuring said ambient temperature value
includes a thermistor coupled to said processor means.

55

9. Apparatus for correcting ambient temperature effect in biosensors as recited in claim 7 wherein said means for cal-
culating said analyte concentration value includes means for solving a polynomial equation; said polynomial equa-
tion including said measured ambient temperature value.

9

EP 0 878 713 A2

10. Apparatus for correcting ambient temperature effect in biosensors as recited in claim 7 wherein said polynomial
equation includes a converted measured current value and predefined experimentally determined coefficients.

11. Apparatus for correcting ambient temperature effect in biosensors as recited in claim 7 wherein said means for cal-
culating said analyte concentration value includes means for converting said measured current to an observed ana-
lyte concentration value and for calculating a corrected analyte concentration value utilizing the equation:

G _ G 1 -(T 2 2 -24 2 )M2-(T 2 >24)M1
2 (T 2 2 -24 2 )* S2 + (T 2 -24)*S1 + 1

where is said observed analyte concentration value, T 2 is said measured ambient temperature value and 11 12
SI, and S2 are set values. ' '

12. Apparatus for correcting ambient temperature effect in biosensors as recited in claim 11 wherein II 12 S1 andS2
are experimentally determined coefficients.

13. Apparatus for correcting ambient temperature effect in biosensors as recited in claim 7 wherein the analyte is Glu-
cose. a

14. Apparatus for correcting ambient temperature effect in biosensors as recited in claim 7 wherein said means respon-
sive to said applied sample to the biosensors, for measuring said current generated in the test sample includes
processor means coupled to the biosensors for receiving a signal representing said current generated in the test
sample.

1 5. Apparatus for correcting ambient temperature effect in biosensors as recited in claim 7 wherein said means for cal-
culating said analyte concentration value includes processor means coupled to said ambient temperature measur-
ing means and said current measuring means and including means for solving a predetermined equation utilizing
said measured values and predetermined coefficient values.

16. A biosensor comprising:

biosensors means for receiving a user sample;

processor means responsive to said user sample receiving means, for measuring a current generated in the
test sample;

means for measuring an ambient temperature value; and

means for calculating an analyte concentration value utilizing said measured ambient temperature value to
thereby increase the accuracy of the analyte determination.

17. A biosensor as recited in claim 16 wherein said processor means includes means for converting said measured
current to an observed analyte concentration value and for calculating a corrected analyte concentration value uti-
lizing the equation:

Q _ G 1 -(T 2 2 -24 2 )*I2-(T 2 -24)M1
(T 2 2 -24 2 )* S2 + (T 2 -24)*S1 + 1

where ^ is said observed analyte concentration value. T 2 is said measured ambient temperature value and 11 12
S1, and S2 are set values.

18. A biosensor as recited in claim 17 wherein 11, 12, S1, and S2 are experimentally determined coefficients.

19. A biosensor as recited in claim 16 wherein said means for measuring said ambient temperature value include a
thermistor coupled to said processor means.

10

EP 0 878 713 A2

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CM

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V

EP0878713 A2

FIG.2

( START
V 200

MEASURE INSTRUMENT
TEMPERATURE T2
202

J

MEASURE
SENSOR
CURRENT J2
204

♦ .

CONVERT CURRENT J2 INTO GLUCOSE
CONCENTRATION G1:
G1=INT+SL0PE\J2
206

_*_ .

CORRECT TEMPERATURE EFFECT
NEW GLUCOSE CONCENTRATION G2:

02=(G1-Cr2*-20*l2-(T2-24riiy

((T2 2 -24 2 )*S2+(T2-24)*S1+1)
208

12